Recent progress in microbial production of succinic acid

doi:10.11949/0438-1157.20191430

Abstract

Abstract:

Succinic acid is considered to be a promising bio-based platform compound due to its potential value in the chemical industry for its C₄ molecular structure. This article comprehensively analyzed the domestic and foreign scholars research status of succinic acid in three aspects which were production strains and strain transformation, biological process optimization and separation process of succinic acid. It emphatically introduced the main production strains and their modification strategies, such as Escherichia coli, Actinobacillus succinogenes and Yarrowia lipolytica. It included the biological process optimization programs such as low biomass utilization, two stages and low pH fermentation strategy and CO₂ supply and pH regulation during fermentation. And it also included the separation process of succinic acid such as calcium salt method, electrodialysis method and direct separation method. At the same time, it pointed out that the emphasis of the future research will be to comprehensively consider the economic and energy consumption issues, integrate the whole process of strain fermentation and separation, increase the yield of succinic acid, reduce the cost of fermentation and separation and then to further expand the market of bio-based succinic acid.

Key words: succinic acid, fermentation, production strain, metabolic engineering, bioprocess, downstream process

摘要：

丁二酸因其C₄分子结构在化工领域的潜在价值，被认为是一种具有广阔应用前景的生物基平台化合物。结合生物基丁二酸的产业现状，综合分析了丁二酸生产菌种及菌株改造、生物过程优化和丁二酸分离纯化这三个方面的研究现状。重点介绍以大肠杆菌、产琥珀酸放线杆菌、解脂耶氏酵母为代表的主要生产菌株及其改造策略；低值生物质利用及控制发酵过程中CO₂ 供给和pH 调节等生物过程优化策略；包括钙盐法、电渗析法、直接分离法等方法在内的丁二酸分离工艺。同时指出未来的研究重点将综合考虑经济性与能耗问题，将菌株与发酵和分离全过程整合，提高丁二酸产量，降低发酵及分离成本，进一步拓展生物基丁二酸市场应用领域。

关键词: 丁二酸, 发酵, 生产菌株, 代谢工程, 生物过程, 下游过程

CLC Number:

Q 599

Yao ZHANG, Xiaoman QIU, Chengpeng CHEN, Zhuoran YU, Housheng HONG. Recent progress in microbial production of succinic acid[J]. CIESC Journal, 2020, 71(5): 1964-1975.

张耀, 邱晓曼, 陈程鹏, 于卓然, 洪厚胜. 生物法制造丁二酸研究进展[J]. 化工学报, 2020, 71(5): 1964-1975.

Figures/Tables 4

References 86

1	Bozell J J, Petersen G R. Technology development for the production of biobased products from biorefinery carbohydrates—the US Department of Energy s “Top 10” revisited[J]. Green Chemistry, 2010, 12(4): 539-554.
2	Werpy T, Petersen G. Top value added chemicals from biomass: volume Ⅰ: results of screening for potential candidates from sugars and synthesis gas[R]. Golden, CO (US): National Renewable Energy Lab., 2004.
3	Yang L, Lübeck M, Lübeck P S. Aspergillus as a versatile cell factory for organic acid production[J]. Fungal Biology Reviews, 2016, 31(1): 33-49.
4	Zeikus J G, Jain M K, Elankovan P. Biotechnology of succinic acid production and markets for derived industrial products[J]. Applied Microbiology and Biotechnology, 1999, 51(5): 545-552.
5	Mika L T, Cséfalvay E, Á Németh. Catalytic conversion of carbohydrates to initial platform chemicals: chemistry and sustainability[J]. Chemical Reviews, 2018, 118(2): 505-613.
6	Bechthold I, Bretz K, Kabasci S, et al. Succinic acid: a new platform chemical for biobased polymers from renewable resources[J]. Chemical Engineering & Technology, 2010, 31(5): 647-654.
7	Pinazo J M, Domine M E, Parvulescu V, et al. Sustainability metrics for succinic acid production: a comparison between biomass-based and petrochemical routes[J]. Catalysis Today, 2015, 239: 17-24.
8	de Jong E, Higson A, Walsh P, et al. Product developments in the bio-based chemicals arena[J]. Biofuels, Bioproducts and Biorefining, 2012, 6(6): 606-624.
9	Gao Y. Method for production of succinic acid and sulfuric acid by paired electrosynthesis: US20130134047 [P].
10	Steinmann S N, Michel C, Schwiedernoch R, et al. Electro-carboxylation of butadiene and ethene over Pt and Ni catalysts[J]. Journal of Catalysis, 2016, 343: 240-247.
11	Cardoso D S P, Aljukić B, Santos D M F, et al. Organic electrosynthesis: from laboratorial practice to industrial applications[J]. Organic Process Research & Development, 2017, 21(9): 1213-1226.
12	Becker J, Reinefeld J, Stellmacher R, et al. Systems‐wide analysis and engineering of metabolic pathway fluxes in bio‐succinate producing Basfia succiniciproducens[J]. Biotechnology & Bioengineering, 2013, 110(11): 3013-3023.
13	Salvachua D, Smith H, St John P C, et al. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens[J]. Bioresource Technology, 2016, 214: 558-566.
14	Jansen M L, van Gulik W M. Towards large scale fermentative production of succinic acid[J]. Current Opinion in Biotechnology, 2014, 30: 190-197.
15	Cok B, Tsiropoulos I, Roes A L, et al. Succinic acid production derived from carbohydrates: an energy and greenhouse gas assessment of a platform chemical toward a bio-based economy[J]. Biofuels Bioproducts & Biorefining, 2014, 8(1): 16-29.
16	Corma A, Iborra S, Velty A. Chemical routes for the transformation of biomass into chemicals[J]. Chemical Reviews, 2007, 107(6): 2411-2502.
17	王庆昭, 吴巍, 赵学明. 生物转化法制取琥珀酸及其衍生物的前景分析[J]. 化工进展, 2004, 23(7):794-798
	Wang Q Z, Wu W, Zhao X M. Market analysis for bioconversion of succinic acid and its derivatives[J] Chemical Industry and Engineering Progress, 2004, 23(7): 794-798.
18	Delhomme C, Weuster-Botz D, Kühn F E. Succinic acid from renewable resources as a C₄ building-block chemical—a review of the catalytic possibilities in aqueous media[J]. Green Chemistry, 2009, 11(1): 13-16.
19	Beauprez J J, De Mey M, Soetaert W K. Microbial succinic acid production: natural versus metabolic engineered producers[J]. Process Biochemistry, 2010, 45(7): 1103-1114.
20	Jiang M, Ma J, Wu M. Progress of succinic acid production from renewable resources metabolic and fermentative strategies[J]. Bioresource Technology, 2017, 245: 1710-1717.
21	Yuzbashev T V, Yuzbasheva E Y, Laptev I A, et al. Is it possible to produce succinic acid at a low pH?[J]. Bioengineered Bugs, 2011, 2(2): 115-119.
22	Gao C, Yang X, Wang H, et al. Robust succinic acid production from crude glycerol using engineered Yarrowia lipolytica[J]. Biotechnology for Biofuels, 2016, 9(1): 179.
23	Li C, Ong K L, Yang X, et al. Bio-refinery of waste streams for green and efficient succinic acid production by engineered Yarrowia lipolytica without pH control[J]. Chemical Engineering Journal, 2019, 371: 804-812.
24	van de Graaf M J, Vallianpoer F, Fiey G, et al. Process for the crystallization of succinic acid: EP2371802A1 [P]. 2011-10-05.
25	Chen K, Li J, Ma J, et al. Succinic acid production by Actinobacillus succinogenes using hydrolysates of spent yeast cells and corn fiber[J]. Bioresource Technology, 2011, 102(2): 1704-1708.
26	Thuy N T H, Kongkaew A, Flood A, et al. Fermentation and crystallization of succinic acid from Actinobacillus succinogenes ATCC55618 using fresh cassava root as the main substrate[J]. Bioresource Technology, 2017, 233: 342-352.
27	Yu Y, Zhu X, Xu H, et al. Construction of an energy-conserving glycerol utilization pathways for improving anaerobic succinate production in Escherichia coli[J]. Metabolic Engineering, 2019, 56: 181-189.
28	Zhu X, Tan Z, Xu H, et al. Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli[J]. Metabolic Engineering, 2014, 24: 87-96.
29	Wei L N, Zhu L W, Tang Y J. Succinate production positively correlates with the affinity of the global transcription factor Cra for its effector FBP in Escherichia coli[J]. Biotechnology for Biofuels, 2016, 9: 264.
30	Litsanov B, Brocker M, Bott M. Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate[J]. Applied and Environmental Microbiology, 2012, 78(9): 3325-3337.
31	Chung S, Park J, Yun J, et al. Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum[J]. Metabolic Engineering, 2017, 40: 157-164.
32	姜岷, 马江锋, 陈可泉, 等. 重组大肠杆菌产琥珀酸研究进展[J]. 微生物学通报, 2009, 36(1):120-124
	Jiang M, Ma J F, Chen K Q, et al. The progress of recombinant Escherichia coli for production of succinic acid[J]. Microbiology China, 2009, 36(1): 120-124.
33	Lin H, Bennett G N, San K Y. Metabolic engineering of aerobic succinate production systems in Escherichia coli to improve process productivity and achieve the maximum theoretical succinate yield[J]. Metabolic Engineering, 2005, 7(2): 116-127.
34	Gokarn R R, Eiteman M A, Altman E. Metabolic analysis of Escherichia coli in the presence and absence of the carboxylating enzymes phosphoenolpyruvate carboxylase and pyruvate carboxylase[J]. Applied & Environmental Microbiology, 2000, 66(5): 1844-1850.
35	Kim P, Laivenieks M, Vieille C, et al. Effect of overexpression of Actinobacillus succinogenes phosphoenolpyruvate carboxykinase on succinate production in Escherichia coli[J]. Appl. Environ. Microbiol., 2004, 70(2): 1238-1241.
36	Singh A, Soh K C, Hatzimanikatis V, et al. Manipulating redox and ATP balancing for improved production of succinate in E. coli[J]. Metabolic Engineering, 2011, 13(1): 76-81.
37	Zhang X, Jantama K, Moore J C, et al. Metabolic evolution of energy-conserving pathways for succinate production in Escherichia coli[J]. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(48): 20180-20185.
38	Gokarn R R, Eiteman M A, Altman E. Expression of pyruvate carboxylase enhances succinate production in Escherichia coli without affecting glucose uptake[J]. Biotechnology Letters, 1998, 20(8): 795-798.
39	Vemuri G N, Eiteman M A, Altman E. Effects of growth mode and pyruvate carboxylase on succinic acid production by metabolically engineered strains of Escherichia coli[J]. Applied & Environmental Microbiology, 2002, 68(4): 1715-1727.
40	Okino S, Noburyu R, Suda M, et al. An efficient succinic acid production process in a metabolically engineered Corynebacterium glutamicum strain[J]. Applied Microbiology and Biotechnology, 2008, 81(3): 459-464.
41	Wang Q, Chen X, Yang Y, et al. Genome-scale in silico aided metabolic analysis and flux comparisons of Escherichia coli to improve succinate production[J]. Applied Microbiology and Biotechnology, 2006, 73(4): 887-894.
42	Sánchez A M, Bennett G N, San K Y. Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity[J]. Metabolic Engineering, 2005, 7(3): 229-239.
43	Balzer G J, Thakker C, Bennett G N, et al. Metabolic engineering of Escherichia coli to minimize byproduct formate and improving succinate productivity through increasing NADH availability by heterologous expression of NAD⁺-dependent formate dehydrogenase[J]. Metabolic Engineering, 2013, 20: 1-8.
44	Donnelly M I, Millard C S, Clark D P, et al. A novel fermentation pathway in an Escherichia coli mutant producing succinic acid, acetic acid, and ethanol[J]. Applied Biochemistry and Biotechnology, 1998, 70/71/72(1): 187-198.
45	梁丽亚, 马江锋, 刘嵘明, 等. 过量表达苹果酸脱氢酶对大肠杆菌NZN111产丁二酸的影响[J]. 生物工程学报, 2011, 27(7):1005-1012.
	Liang L Y, Ma J F, Liu R M, et al. Effect of overexpression of malate dehydrogenase on succinic acid production in Escherichia coli NZN111[J]. Chin. J. Biotech., 2011, 27(7): 1005-1012.
46	Bunch P K, Mat-Jan F, Lee N, et al. The IdhA gene encoding the fermentative lactate dehydrogenase of Escherichia coli[J]. Microbiology, 1997, 143 (1): 187.
47	Jantama K, Haupt M J, Svoronos S A, et al. Combining metabolic engineering and metabolic evolution to develop nonrecombinant strains of Escherichia coli C that produce succinate and malate[J]. Biotechnology and Bioengineering, 2008, 99(5): 1140-1153.
48	Jantama K, Zhang X, Moore J C, et al. Eliminating side products and increasing succinate yields in engineered strains of Escherichia coli C[J]. Biotechnology & Bioengineering, 2010, 101(5): 881-893.
49	Ahn J H, Jang Y S, Sang Y L. Production of succinic acid by metabolically engineered microorganisms[J]. Current Opinion in Biotechnology, 2016, 42: 54-66.
50	McKinlay J B, Laivenieks M, Schindler B D, et al. A genomic perspective on the potential of Actinobacillus succinogenes for industrial succinate production[J]. BMC Genomics, 2010, 11: 680.
51	Zheng P, Zhang K, Yan Q, et al. Enhanced succinic acid production by Actinobacillus succinogenes after genome shuffling[J]. Journal of Industrial Microbiology & Biotechnology, 2013, 40(8): 831-840.
52	Mckinlay J B, Zeikus J G, Vieille C. Insights into Actinobacillus succinogenes fermentative metabolism in a chemically defined growth medium[J]. Applied and Environmental Microbiology, 2005, 71(11): 6651-6656.
53	Choi S, Song C W, Shin J H, et al. Biorefineries for the production of top building block chemicals and their derivatives[J]. Metabolic Engineering, 2015, 28: 223-239.
54	Sandstrom A G, Almqvist H, Portugal-Nunes D, et al. Saccharomyces cerevisiae: a potential host for carboxylic acid production from lignocellulosic feedstock?[J]. Applied Microbiology and Biotechnology, 2014, 98(17): 7299-7318.
55	Raab A M, Gebhardt G, Bolotina N, et al. Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid[J]. Metabolic Engineering, 2010, 12(6): 518-525.
56	Yan D, Wang C, Zhou J, et al. Construction of reductive pathway in Saccharomyces cerevisiae for effective succinic acid fermentation at low pH value[J]. Bioresource Technology, 2014, 156: 232-239.
57	Li C, Gao S, Yang X, et al. Green and sustainable succinic acid production from crude glycerol by engineered Yarrowia lipolytica via agricultural residue based in situ fibrous bed bioreactor[J]. Bioresource Technology, 2018, 249: 612-619.
58	Beopoulos A, Cescut J, Haddouche R, et al. Yarrowia lipolytica as a model for bio-oil production[J]. Progress in Lipid Research, 2009, 48(6): 375-387.
59	Kamzolova S V, Allayarov R K, Lunina J N, et al. The effect of oxalic and itaconic acids on threo-Ds-isocitric acid production from rapeseed oil by Yarrowia lipolytica[J]. Bioresource Technology, 2016, 206: 128-133.
60	Tomaszewska L, Rywińska A, Gładkowski W. Production of erythritol and mannitol by Yarrowia lipolytica yeast in media containing glycerol[J]. Journal of Industrial Microbiology & Biotechnology, 2012, 39(9): 1333-1343.
61	Nicaud J. Yarrowia lipolytica[J]. Yeast, 2012, 29(10): 409-418.
62	Yuzbashev T V, Yuzbasheva E Y, Sobolevskaya T I, et al. Production of succinic acid at low pH by a recombinant strain of the aerobic yeast Yarrowia lipolytica[J]. Biotechnology and Bioengineering, 2010, 107(4): 673-682.
63	Cui Z, Gao C, Li J, et al. Engineering of unconventional yeast Yarrowia lipolytica for efficient succinic acid production from glycerol at low pH[J]. Metabolic Engineering, 2017, 42: 126-133.
64	Koutinas A A, Vlysidis A, Pleissner D, et al. Valorization of industrial waste and by-product streams via fermentation for the production of chemicals and biopolymers[J]. Chemical Society Reviews, 2014, 43(8): 2587-2627.
65	Zheng P, Dong J, Sun Z, et al. Fermentative production of succinic acid from straw hydrolysate by Actinobacillus succinogenes[J]. Bioresource Technology, 2009, 100(8): 2425-2429.
66	Zhang A Y, Sun Z, Leung C C J, et al. Valorisation of bakery waste for succinic acid production[J]. Green Chemistry, 2013, 15(3): 690.
67	Almeida J R M, Fávaro L C L, Quirino B F. Biodiesel biorefinery: opportunities and challenges for microbial production of fuels and chemicals from glycerol waste[J]. Biotechnology for Biofuels, 2012, 5(1): 48.
68	Liu Y P, Zheng P, Sun Z H, et al. Strategies of pH control and glucose-fed batch fermentation for production of succinic acid by Actinobacillus succinogenes CGMCC1593[J]. Journal of Chemical Technology & Biotechnology, 2008, 83(5): 722-729.
69	Lin H, Bennett G N, San K Y. Fed-batch culture of a metabolically engineered Escherichia coli strain designed for high-level succinate production and yield under aerobic conditions[J]. Biotechnology and Bioengineering, 2005, 90(6): 775-779.
70	Vemuri G N, Eiteman M A, Altman E. Succinate production in dual-phase Escherichia coli fermentations depends on the time of transition from aerobic to anaerobic conditions[J]. Journal of Industrial Microbiology & Biotechnology, 2002, 28(6): 325-332.
71	Wang D, Li Q, Song Z, et al. High cell density fermentation via a metabolically engineered Escherichia coli for the enhanced production of succinic acid[J]. Journal of Chemical Technology & Biotechnology, 2011, 86(4): 512-518.
72	Yan Q, Zheng P, Dong J J, et al. A fibrous bed bioreactor to improve the productivity of succinic acid by Actinobacillus succinogenes[J]. Journal of Chemical Technology & Biotechnology, 2014, 89(11): 1760-1766.
73	Kim M I, Kim N J, Shang L, et al. Continuous production of succinic acid using an external membrane cell recycle system[J]. Journal of Microbiology and Biotechnology, 2009, 19(11): 1369.
74	Wang C, Li Q, Tang H, et al. Membrane fouling mechanism in ultrafiltration of succinic acid fermentation broth[J]. Bioresource Technology, 2012, 116: 366-371.
75	Samuelov N S, Lamed R, Lowe S, et al. Influence of CO₂-HCO₃^- levels and pH on growth, succinate production, and enzyme activities of Anaerobiospirillum succiniciproducens[J]. Appl. Environ. Microbiol., 1991, 57(10): 3013-3019.
76	Lu S, Eiteman M A, Altman E. Effect of CO₂ on succinate production in dual-phase Escherichia coli fermentations[J]. Journal of Biotechnology, 2009, 143(3): 213-223.
77	Andersson C, Helmerius J, Hodge D, et al. Inhibition of succinic acid production in metabolically engineered Escherichia coli by neutralizing agent, organic acids, and osmolarity[J]. Biotechnology Progress, 2009, 25(1): 116-123.
78	Li J, Zheng X, Fang X, et al. A complete industrial system for economical succinic acid production by Actinobacillus succinogenes[J]. Bioresource Technology, 2011, 102(10): 6147-6152.
79	López-Garzón C S, Straathof A J J. Recovery of carboxylic acids produced by fermentation[J]. Biotechnology Advances, 2014, 32(5): 873-904.
80	Mazière A, Prinsen P, García A, et al. A review of progress in (bio) catalytic routes from/to renewable succinic acid[J]. Biofuels, Bioproducts and Biorefining, 2017, 11(5): 908-931.
81	Kurzrock T, Weuster-Botz D. Recovery of succinic acid from fermentation broth[J]. Biotechnology Letters, 2010, 32(3): 331-339.
82	Guettler M V, Jain M K, Soni B K. Process for making succinic acid, microorganisms for use in the process and methods of obtaining the microorganisms: US5723322 [P].1998-3-3.
83	Glassner D A, Datta R. Process for the production and purification of succinic acid: US5143834 [P]. 1992-9-1.
84	Cheng K, Zhao X, Zeng J, et al. Downstream processing of biotechnological produced succinic acid[J]. Applied Microbiology and Biotechnology, 2012, 95(4): 841-850.
85	Luque R, Lin C S, Du C, et al. Chemical transformations of succinic acid recovered from fermentation broths by a novel direct vacuum distillation-crystallisation method[J]. Green Chemistry, 2009, 11(2): 193-200.
86	Li Q, Wang D, Wu Y, et al. One step recovery of succinic acid from fermentation broths by crystallization[J]. Separation and Purification Technology, 2010, 72(3): 294-300.

生产商	产能/(万吨/年)	原料	生产菌株	发酵及分离工艺
Myriant	1.4	糖浆/木质纤维素水解液	E. coli	氨水维持pH，氨沉淀法分离工艺
BioAmber	0.4	麦芽糖浆	E. coli	氢氧化钠维持pH，电透析法分离工艺
BioAmber & Mitsubishi	3.0	玉米糖浆	Candida krusei	低pH发酵，直接结晶工艺
Succinity	1.0	甘油/糖浆	Basfia succiniciproducens	Mg(OH)₂维持pH，镁盐分离工艺
Reverdia	1.0	糖浆	S. cerevisiae	低pH发酵，直接结晶工艺

生产商	产能/(万吨/年)	原料	生产菌株	发酵及分离工艺
Myriant	1.4	糖浆/木质纤维素水解液	E. coli	氨水维持pH，氨沉淀法分离工艺
BioAmber	0.4	麦芽糖浆	E. coli	氢氧化钠维持pH，电透析法分离工艺
BioAmber & Mitsubishi	3.0	玉米糖浆	Candida krusei	低pH发酵，直接结晶工艺
Succinity	1.0	甘油/糖浆	Basfia succiniciproducens	Mg(OH)₂维持pH，镁盐分离工艺
Reverdia	1.0	糖浆	S. cerevisiae	低pH发酵，直接结晶工艺

菌株	发酵方式	丁二酸产量/(g /L)	碳源	得率/(g/g)	生产速率/(g /( L·h))	Ref.
Y. lipolytica Y-3314	通氧	45.5	葡萄糖	-	-	[21]
Y. lipolytica PGC01003	通氧	160.2	粗甘油	0.40	0.40	[22]
Y. lipolytica PGC202	通氧；低pH	71.6	混合食物废弃物	0.61	0.40	[23]
S. cerevisiae	通氧	45.00	葡萄糖	-	0.45	[24]
A. succinogenes NJ113	厌氧	47.5	玉米芯水解液	0.68	0.63	[25]
A. succinogenes ATCC 55618	厌氧	151.44	木薯根水解液	1.51	3.22	[26]
E. coli YY-GS004	厌氧	57	甘油	1.28	0.59	[27]
E. coli AFP111	两阶段发酵	101.2	葡萄糖	1.1	1.3	[28]
E. coli Tang 1683	两阶段发酵	92.7	葡萄糖	0.73	1.25	[29]
C. glutamicum BOL-2	两阶段发酵	133.8	葡萄糖	1.10	2.48	[30]
C. glutamicum S071	厌氧	152.2	葡萄糖	1.10	1.11	[31]

菌株	发酵方式	丁二酸产量/(g /L)	碳源	得率/(g/g)	生产速率/(g /( L·h))	Ref.
Y. lipolytica Y-3314	通氧	45.5	葡萄糖	-	-	[21]
Y. lipolytica PGC01003	通氧	160.2	粗甘油	0.40	0.40	[22]
Y. lipolytica PGC202	通氧；低pH	71.6	混合食物废弃物	0.61	0.40	[23]
S. cerevisiae	通氧	45.00	葡萄糖	-	0.45	[24]
A. succinogenes NJ113	厌氧	47.5	玉米芯水解液	0.68	0.63	[25]
A. succinogenes ATCC 55618	厌氧	151.44	木薯根水解液	1.51	3.22	[26]
E. coli YY-GS004	厌氧	57	甘油	1.28	0.59	[27]
E. coli AFP111	两阶段发酵	101.2	葡萄糖	1.1	1.3	[28]
E. coli Tang 1683	两阶段发酵	92.7	葡萄糖	0.73	1.25	[29]
C. glutamicum BOL-2	两阶段发酵	133.8	葡萄糖	1.10	2.48	[30]
C. glutamicum S071	厌氧	152.2	葡萄糖	1.10	1.11	[31]

[1]	Xuejin GAO, Yuzhuo YAO, Huayun HAN, Yongsheng QI. Fault monitoring of fermentation process based on attention dynamic convolutional autoencoder [J]. CIESC Journal, 2023, 74(6): 2503-2521.
[2]	Chunlei ZHAO, Liang GUO, Cong GAO, Wei SONG, Jing WU, Jia LIU, Liming LIU, Xiulai CHEN. Metabolic engineering of Escherichia coli for chondroitin production [J]. CIESC Journal, 2023, 74(5): 2111-2122.
[3]	Zhuotao TAN, Siyu QI, Mengjiao XU, Jie DAI, Chenjie ZHU, Hanjie YING. Application of the redox cascade systems with coenzyme self-cycling in biocatalytic processes: opportunities and challenges [J]. CIESC Journal, 2023, 74(1): 45-59.
[4]	Xue LIU, Lijuan ZHANG, Guangrong ZHAO. Commensalistic Escherichia coli coculture for biosynthesis of daidzein [J]. CIESC Journal, 2022, 73(9): 4015-4024.
[5]	Yuelin WANG, Wei CHAO, Xiaocheng LAN, Zhipeng MO, Shuhuan TONG, Tiefeng WANG. Review of ethanol production via biological syngas fermentation [J]. CIESC Journal, 2022, 73(8): 3448-3460.
[6]	Xuejin GAO, Zihe HE, Huihui GAO, Yongsheng QI. Quality-related fault monitoring of multi-phase fermentation process based on joint canonical variable matrix [J]. CIESC Journal, 2022, 73(3): 1300-1314.
[7]	Xinye HUANG, Ye ZHANG, Shuyuan ZHANG, Zhen CHEN, Tong QIU. Application of Bayesian optimization method in the production of 1,3-propanediol by Vibrio natriegens [J]. CIESC Journal, 2022, 73(11): 5039-5046.
[8]	Wulin ZHOU, Huifang GAO, Yuling WU, Xian ZHANG, Meijuan XU, Taowei YANG, Minglong SHAO, Zhiming RAO. Engineering of Saccharomyces cerevisiae for biosynthesis of campesterol [J]. CIESC Journal, 2021, 72(8): 4314-4324.
[9]	YANG Ruixiong, ZHENG Xin, LU Tao, ZHAO Yuze, YANG Qinghua, LU Yinghua, HE Ning, LING Xueping. Effects of substitution of ER domains on the synthesis of eicosapentaenoic acid in Schizochytrium limacinum SR21 [J]. CIESC Journal, 2021, 72(7): 3768-3779.
[10]	LIU Cong, XIE Li, YANG Huizhong. Multi-model soft sensor development for penicillin fermentation process based on improved density peak clustering [J]. CIESC Journal, 2021, 72(3): 1606-1615.
[11]	Yukun ZHENG, Qing SUN, Zhen CHEN, Huimin YU. Progress for chemicals production via microbial cell factory: selecting several small molecules and macromolecular products as examples [J]. CIESC Journal, 2021, 72(12): 6109-6121.
[12]	Yanfang WANG,Heng MAO,Weiwei CAI,Aoshuai ZHANG,Lihao XU,Zhiping ZHAO. Enhancing ethanol production efficiency by ZIF-L/PDMS mixed matrix membrane via vapor permeation-fermentation coupling process [J]. CIESC Journal, 2021, 72(10): 5226-5236.
[13]	WANG Kaifeng, WANG Jinpeng, WEI Ping, JI Xiaojun. Metabolic engineering of Yarrowia lipolytica to produce fatty acids and their derivatives [J]. CIESC Journal, 2021, 72(1): 351-365.
[14]	Yanru PAN, Fei LIU. Estimation of microbial metabolic state based on hybrid cybernetic model [J]. CIESC Journal, 2020, 71(7): 3165-3171.
[15]	Shan HUANG, Yongze LU, Guangcan ZHU, Yun KONG. Construction and operation of MLMB -MFC coupled with biocathode SND [J]. CIESC Journal, 2020, 71(4): 1772-1780.